Background:  ART has improved the survival of children with perinatal HIV infection, and survival is often associated with improvement of thymic function and immune reconstitution. Persisting HIV-specific cell-mediated immune responses have been observed in some patients with undetectable viral load, suggestive of ongoing viral replication. It is unclear whether immune reconstitution is compromised in subjects with incomplete suppression of HIV-1 replication.

Methods:  We examined CD4⁺ T cell counts, thymus volume, and T cell receptor recombination excision circle (TREC) values in 43 perinatally infected adolescents and adults (PI-A) and 28 age-matched seronegative controls:  10 PI-A (14.2 to 20.8 years) with undetectable viral load and 6 age-matched seronegative subjects were chosen for T cell receptor analysis. A real-time polymerase chain reaction (RT-PCR) based quantitative T cell receptor (TCR) Vb spectra-typing approach was used to examine the breadth of TCR repertoire in CD4⁺CD45RA⁺CD31⁺ and CD8⁺CD45RA⁺CD28⁺ T cell subsets. HIV-specific CD8 T cell responses were quantitated by ELISpot.

Results:  Total CD4⁺ T cell counts, thymus volume, and TREC values were similar between the seropositive and the age-matched controls. CD4⁺CD45RA⁺CD31⁺ T cells, thought to be recent thymic emigrants, were also similar in number in the PI-A and control subjects (mean 340 vs 305 cells/µL, respectively; p = 0.25). CDR3 length analysis allowed division of the entire TCR Vb repertoire into 205 discrete measurements. Perturbation of TCR repertoire in each naïve T cell subset was defined as a change in a TCR population to either 2 standard deviations above or below the means expression level seen in seronegative controls. PI-A subjects had greater numbers of overall perturbations in both the naïve CD4 T cells (p <0.05) and naïve CD8 T (p <0.05) compare to controls. There was a trend between HIV-specific CTL responses and the degrees of perturbation in CD31⁺ naïve CD4 T cell subset in these subjects (R² = 0.3, p = 0.1). 

Conclusions:  Although most parameters of thymopoiesis appear to be normal in the aviremic HIV seropositive youths, the perturbations observed in the TCR repertoire suggest ongoing HIV replication is continuing to have a detrimental effect on T cell production. These data illustrate the complex relationship between viral replication and thymopoiesis. Intensified therapy may be needed to promote long-term preservation of T cell populations with a diverse TCR repertoire.